Circulating levels of 3‐hydroxymyristate, a direct quantification of endotoxaemia in noninfected cirrhotic patients

Weil, Delphine; Barros, Jean‐Paul Pais de; Mourey, Guillaume; Laheurte, Caroline; Cypriani, Benoit; Badet, N.; Delabrousse, Éric; Grandclément, Émilie; Martino, Vincent Di; Saas, Philippe; Lagrost, Laurent; Thévenot, Thierry

doi:10.1111/liv.13916

Cited by 8 publications

(7 citation statements)

References 44 publications

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“…23 Such a technique has been validated in patients with cirrhosis. 22 Herein, we confirm that patients with SAH have higher endotoxemia than patients with cirrhosis and controls. 30 The weak although significant correlation between sST2 levels and MELD score or endotoxemia suggests that liver failure and latent infection do not play an exclusive role to drive sST2 up in patients with SAH.…”

Section: Discussionsupporting

confidence: 72%

“…A total of 161 patients with SAH, 72 with severe cirrhosis and 28 healthy controls were included in the different analyses in the study. The main patient characteristics at inclusion are reported in Table S1 [22][23][24][25][26][27][28][29][30][31] vs. 20 [17][18][19][20][21][22][23][24][25][26], p <0.0001, respectively); however, Child-Pugh score (11 [10][11][12] vs. 10 [8][9][10][11][12][13], p = 0.3) and 2-month survival (71.9 [65-78.8] vs. 66.6 [55.5-77.8], p = 0.22) were not different between the 2 groups.…”

Section: Resultsmentioning

confidence: 99%

“…Endotoxemia was assessed using HPLC-MS/MS (high-performance liquid chromatography coupled with mass spectrometry) to detect 3-hydroxymyristate (3-HM), a lipid component of LPS, in the serum of controls, patients with cirrhosis and patients with SAH. Methods are described in detail in Weil et al and Pais de Barros et al 22,23 Immunocytochemistry for GRK2 Two-hundred thousand PMNs were fixed with cold methanol for 30 s on Cytospin slides. Slides were incubated (or not as negative controls) overnight at 4 C with primary anti-GRK2 polyclonal rabbit antibody (ref.…”

Section: Quantification Of Endotoxemiamentioning

confidence: 99%

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IL-33/ST2 pathway regulates neutrophil migration and predicts outcome in patients with severe alcoholic hepatitis

Artru

Saleh

Maggiotto

et al. 2020

Journal of Hepatology

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Graphical abstractSevere alcoholic hepatitis Decoy receptor sST2 HighlightsThe IL-33/ST2 pathway is defective in the neutrophils of patients with severe alcoholic hepatitis.This defect is associated with a higher risk of developing infection.Dosage of the decoy receptor sST2 helps identify patients at risk of death and/or infection.The defect in IL-33/ST2 in neutrophils is responsible for lower migration capacities.Treating neutrophils with recombinant IL-33 restores, at least in part, their migration capacities.

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Section: Discussionsupporting

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Section: Quantification Of Endotoxemiamentioning

confidence: 99%

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IL-33/ST2 pathway regulates neutrophil migration and predicts outcome in patients with severe alcoholic hepatitis

Artru

Saleh

Maggiotto

et al. 2020

Journal of Hepatology

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“…These included metabolites that were previously reported in association with insulin resistance and T2DM such as glucose and 1,5-AG [37, 38]. Other identified metabolites were reported in association with comorbidities of insulin resistance and T2DM including fatty acid metabolic disorders (such as 3-hydroxylaurate) [39], impairment of liver function and diabetic status (such as 3-hydroxymyristate and homoarginine) [40, 41] and vascular disease (such as dimethylarginine) [42]. Other novel arginine metabolites were also found to be significantly changed with disease progression including ornithine (a precursor of arginine, also a medication for hepatic encephalopathy) [43] and 2-oxoarginine (a metabolite of arginine catabolism and a marker of argininemia) [44].…”

Section: Discussionmentioning

confidence: 99%

Metabolic signature of obesity-associated insulin resistance and type 2 diabetes

et al. 2019

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BackgroundObesity is associated with an increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). However, some obese individuals maintain their insulin sensitivity and exhibit a lower risk of associated comorbidities. The underlying metabolic pathways differentiating obese insulin sensitive (OIS) and obese insulin resistant (OIR) individuals remain unclear.MethodsIn this study, 107 subjects underwent untargeted metabolomics of serum samples using the Metabolon platform. Thirty-two subjects were lean controls whilst 75 subjects were obese including 20 OIS, 41 OIR, and 14 T2DM individuals.ResultsOur results showed that phospholipid metabolites including choline, glycerophosphoethanolamine and glycerophosphorylcholine were significantly altered from OIS when compared with OIR and T2DM individuals. Furthermore, our data confirmed changes in metabolic markers of liver disease, vascular disease and T2DM, such as 3-hydroxymyristate, dimethylarginine and 1,5-anhydroglucitol, respectively.ConclusionThis pilot data has identified phospholipid metabolites as potential novel biomarkers of obesity-associated insulin sensitivity and confirmed the association of known metabolites with increased risk of obesity-associated insulin resistance, with possible diagnostic and therapeutic applications. Further studies are warranted to confirm these associations in prospective cohorts and to investigate their functionality.

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“…This method measures total circulating LPS, including bound and unbound LPS to lipoproteins and not only LPS activity (i.e., unbound LPS able to activate the LAL assay). This has been used in different pathological settings (25,26). Yet, the quantification of LPS subtypes according to the length of lipid A carbon chains (3OHC12:0, 3OHC14:0, 3OHC16:0 or 3OHC18:0) has never been tested in a pathogenic setting.…”

Section: Introductionmentioning

confidence: 99%

New Insights on End-Stage Renal Disease and Healthy Individual Gut Bacterial Translocation: Different Carbon Composition of Lipopolysaccharides and Different Impact on Monocyte Inflammatory Response

et al. 2021

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Chronic kidney disease induces disruption of the intestinal epithelial barrier, leading to gut bacterial translocation. Here, we appreciated bacterial translocation by analyzing circulating lipopolysaccharides (LPS) using two methods, one measuring only active free LPS, and the other quantifying total LPS as well as LPS lipid A carbon chain length. This was done in end-stage renal disease (ESRD) patients and healthy volunteers (HV). We observed both higher LPS concentration in healthy volunteers and significant differences in composition of translocated LPS based on lipid A carbon chain length. Lower LPS activity to mass ratio and higher concentration of high-density lipoproteins were found in HV, suggesting a better plasma capacity to neutralize LPS activity. Higher serum concentrations of soluble CD14 and pro-inflammatory cytokines in ESRD patients confirmed this hypothesis. To further explore whether chronic inflammation in ESRD patients could be more related to LPS composition rather than its quantity, we tested the effect of HV and patient sera on cytokine secretion in monocyte cultures. Sera with predominance of 14-carbon chain lipid A-LPS induced higher secretion of pro-inflammatory cytokines than those with predominance of 18-carbon chain lipid A-LPS. TLR4 or LPS antagonists decreased LPS-induced cytokine production by monocytes, demonstrating an LPS-specific effect. Thereby, septic inflammation observed in ESRD patients may be not related to higher bacterial translocation, but to reduced LPS neutralization capacity and differences in translocated LPS subtypes.

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Circulating levels of 3‐hydroxymyristate, a direct quantification of endotoxaemia in noninfected cirrhotic patients

Cited by 8 publications

References 44 publications

IL-33/ST2 pathway regulates neutrophil migration and predicts outcome in patients with severe alcoholic hepatitis

IL-33/ST2 pathway regulates neutrophil migration and predicts outcome in patients with severe alcoholic hepatitis

Metabolic signature of obesity-associated insulin resistance and type 2 diabetes

New Insights on End-Stage Renal Disease and Healthy Individual Gut Bacterial Translocation: Different Carbon Composition of Lipopolysaccharides and Different Impact on Monocyte Inflammatory Response

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